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Cell generation within human thymic subsets defined by selective expression of CD45 (T200) isoforms.

M Egerton1, E Pruski, L M Pilarski

  • 1Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

Human Immunology
|April 1, 1990
PubMed
Summary

The study identifies a specific thymocyte lineage (CD45 p180-) responsible for generating mature T cells. This lineage, marked by high-molecular-mass CD45 isoforms, contains cycling cells crucial for producing thymic emigrants.

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • The thymus generates T lymphocytes, but most thymocytes undergo programmed cell death.
  • Distinguishing thymocytes destined for death from those that mature has been challenging due to a lack of specific markers.

Purpose of the Study:

  • To investigate the role of CD45 (leukocyte common antigen) isoforms in defining thymocyte lineages.
  • To determine if thymocytes expressing high-molecular-mass CD45 isoforms are actively cycling and capable of generating mature T cells.

Main Methods:

  • Multicolor immunofluorescence and flow cytometry were used to analyze thymocyte subsets.
  • DNA content analysis (7-amino actinomycin D and propidium iodide staining) assessed cell cycle status.
  • Negative depletion methods isolated thymocyte subsets based on CD45 isoforms, CD3, CD4, and CD8 expression.

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Main Results:

  • Thymocytes expressing high-molecular-mass CD45 isoforms (CD45 p180- lineage) showed significant cell cycling.
  • These cycling CD45 p180- thymocytes include major subsets like CD4-(8-) and CD3-(4-)(8-).
  • CD3-/lo thymocytes exhibited high cycling activity, while CD1-/lo thymocytes showed low activity, consistent with murine data.

Conclusions:

  • The CD45 p180- thymocyte lineage, characterized by high-molecular-mass CD45 isoforms, contains a substantial number of cycling cells.
  • Numerical analysis supports the conclusion that this cycling thymocyte fraction is sufficient to generate the daily requirement of mature thymocytes and thymic emigrants.